Various reports have been made up to now on methods for synthesis of 2,4'-dipyridyl, but all of these methods of synthesis involve problems. None of the methods of synthesis are satisfactory.
For example, in the condensation reaction of 4-cyanopyridine and acetylene disclosed in the specification of U.S. Pat. No. 4,196,287, there is the danger of explosion since a high pressure acetylene gas is used, and therefore, special equipment is required, and the method is not generally accepted.
Further, in the Ullmann-like reaction of 2-halopyridine and 4-halopyridine (Khim. Geol. Nauk., vol. 5, p. 114, 1970), 2,2'-dipyridyl and 4,4'-dipyridyl are produced, in addition to the desired 2,4'-dipyridyl, and therefore, the yield is poor.
Further, cross coupling reactions between a halopyridine and various pyridine metal reagents (see Grignard reagent: Synthesis, vol. 7, p. 564, 1986; tin reagents: T. L., vol. 33, no. 16, p. 2199, 1992; borane reagent: Chem. Pharm. Bull., vol. 33, no. 11, p. 4755, 1985) using a palladium catalyst has been reported in numerous conditions, but isomers such as 2,2'-dipyridyl and 4,4'-dipyridyl are produced in large amounts in addition to the desired 2,4'-dipyridyl, and therefore, the yield is poor and the purification is very tedious.
Further, as another method, the reaction with an N-ethoxycarbonyl pyridinium salt (see J. Chin. Chem. Soc. (Taipei), vol. 36, no. 6, p. 609, 1989) was reported, but the yield is extremely poor and in the improved method (see Heterocycle, vol. 31, no. 4, p. 637, 1990), the number of reaction steps is tremendously increased, and therefore, this method is not practical.
There have been other methods reported in literature, but the synthetic routes are long and the yields of all of the processes are low (for example, see T.L., vol. 25, no. 35, p. 3887, 1994 and Pol. J. Chem., vol. 53, no. 4, p. 893, 1979).
As explained above, all of the reported methods of 2,4'-dipyridyl up to now have been poor in yield or have not been easy in operation and were not industrially satisfactory. Further, the simple removal method of the isomers, i.e., 2,2'-dipyridyl or 4,4'-dipyridyl, which were sometimes produced has not been studied at all.